"The hypothesis of hypo-functionality of NMDA receptors in schizophrenia originates from the observation that administration of the NMDA antagonist phencyclidine (PCP) induces psychotic states that closely resemble schizophrenic symptoms and that persist after drug discontinuation. A large number of animal studies have used PCP and the NMDA antagonist dizocilpine (MK-801) almost interchangeably to model schizophrenia," scientists in the United States report (see also Schizophrenia).

"However, PCP interacts with pharmacological targets other than NMDA receptors that are not affected by MK-801. In addition, although acute administration of either compound produces similar effects in animals, there is little information whether withdrawal from chronic MK-801 causes behavioral deficits that mimic schizophrenia symptoms as in the case of PCP," wrote A. Seillier and colleagues, University of Texas.

The researchers concluded: "To clarify this issue, we compared the following behaviors in rats subjected to withdrawal from sub-chronic administration (2 x 7 days) of either PCP (5 mg/kg, i.p.) or MK-801 (0.5 mg/kg, i.p.): (1) working memory in a variable-delayed alternation task in a T-maze, (2) social interaction, and (3) motor activity in response to a (a) novel environment."

Seillier and colleagues published their study in Behavioural Brain Research (Evaluation of NMDA receptor models of schizophrenia: Divergences in the behavioral effects of sub-chronic PCP and MK-801. Behavioural Brain Research, 2009;204(2 Sp. Iss.):410-415).

For additional information, contact A. Seillier, University of Texas Health Science Center San Antonio, Dept. of Pharmacology, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.

The publisher's contact information for the journal Behavioural Brain Research is: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands.